Clinical characteristics and statin eligibility of patients under 50 with ST‐elevation myocardial infarction

Abstract Aims This study seeks to understand the clinical characteristics, risk factors, and statin eligibility of younger adults who present with STEMI. Methods We performed a retrospective analysis of a prospective cohort of STEMI patients <50 years. Baseline characteristics, medical history, prior medications, drug use, lipid profiles, cardiovascular risk factors were examined. Ten‐year ASCVD risk was calculated utilizing the Pooled Cohort Equations. Statin eligibility was determined according to the 2019 American College of Cardiology (ACC)/American Heart Association (AHA) and the 2022 US Preventive Services Task Force (USPSTF) guidelines. Results Six hundred and thirty‐five individuals were included, the majority were men (82.4%) and white (89%), with a median age was 46.9 [42.0–48.0]. The most prevalent risk factors were current smoking (59%), hyperlipidemia (44%), and hypertension (37%). Drug use was rare (8.3%). Preventative medication use was low, aspirin was the most common (14%), followed by ACE inhibitors/ARBs (12%), statins (11%), and beta‐blockers (9.1%). Mean HDL‐C was low at 36.4 ± 12.0 mg/dL, while mean LDL was unremarkable at 112.4 ± 37.9 mg/dL. According to the 2019 ACC/AHA guidelines, 45.5% were classified as statin recommended, 8.7% were classified as statin considered, and 45.8% were classified as statin not recommended. According to the 2022 USPSTF guidelines, 29% were classified as statin recommended, 12.4% were classified as statin considered, and 58.6% were classified as statin not recommended. Conclusions Younger adults with STEMI exhibit high rates of tobacco use and low rates of preventative medications use. Approximately half of the cohort did not meet criteria for statin initiation.


| INTRODUCTION
Advances in cardiovascular prevention have led to a decrease in hospitalizations for acute myocardial infarction (MI) in the US over the past few decades. 1,24][5] One reason for this may be the earlier development of obesity and its associated cardiovascular risk factors.Multiple studies have demonstrated the increasing prevalence of obesity in adolescents and younger adults, 6,7 which is strongly associated with continued obesity in adulthood. 8This leads to earlier development of cardiometabolic risk factors including hyperlipidemia, hypertriglyceridemia, hypertension, and elevated blood glucose. 9Chronic exposure to these risk factors at earlier ages increases the risk of developing premature atherosclerotic cardiovascular disease (ASCVD).Younger individuals are less likely to undergo cardiovascular risk assessment and are less likely to be eligible for preventative therapies when they do undergo assessment. 10Ultimately, this allows the development of clinical ASCVD that may otherwise be attenuated. 11-elevation myocardial infarction (STEMI) is a unique subset of MI associated with a high risk for morbid cardiovascular complications and therefore warrants emergent treatment regardless of age.Prevention of STEMI remains of utmost importance to the maintenance of optimal cardiovascular health.To optimize the approach to prevention of STEMI in younger adults, a better understanding of the demographics and risk factors in this population is needed.In this analysis, we sought to determine the clinical characteristics of young STEMI patients (<50 years), their cardiovascular risk at the time of STEMI, and their pre-STEMI eligibilty for lipid-lowering therapy utilizing data from a large contemporary cohort of patients treated in a regional STEMI system.

| Study design and patients
The Minneapolis Heart Institute (MHI) regional STEMI program includes Abbott Northwestern Hospital in Minneapolis, MN as well as over 20 regional hospitals. 12 was reviewed and those that did not meet the above STEMI criteria were excluded.For patients who had multiple admissions meeting criteria for STEMI, the first admission was considered the index admission for this analysis.This study was funded entirely by the Minneapolis Heart Institute Research Foundation.Institutional review board approval was obtained before data collection and data analysis.No data were collected on patients who had not consented to allow their clinical data to be used for research purposes.

| Data collection
Patient baseline factors including age, sex, race, height, weight, systolic blood pressure, and hemoglobin a1c% were collected from the electronic health record (EHR).Body mass index (BMI) was calculated from the individual's weight in kilograms and height in meters.Hemoglobin A1c% values within 6 months of the patient's index admission were included in this study.Histories of coronary artery disease (CAD), MI, PCI, coronary artery bypass graft surgery (CABG), stroke, hypertension, hyperlipidemia, diabetes, and family history of CAD were collected from the EHR and confirmed by the admitting physician during the admission interview.Home medications were collected from the EHR and were verified with either the patient or with the patient's outpatient pharmacy by a registered nurse.If this was not possible, the patient's primary care physician was contacted to verify the patient's home medications.A history of drug use was ascertained by the admitting physician during the admission interview and confirmed by reviewing prior urine drug screen results from the EHR.The decision to check a urine drug screen during the index admission was determined by the treating physician.Total cholesterol, LDL-C, HDL-C, and triglycerides drawn within 24 h after the index admission were collected from the EHR.

| Statistical analysis
Baseline characteristics were stratified by sex when possible and compared using Wilcoxon rank-sum tests, Fisher's exact tests, and Pearson's χ 2 tests as appropriate.Categorical variables were presented as frequencies and percentages and continuous variables were summarized as median and interquartile range (IQR).
The 10-year ASCVD risk was calculated by the Pooled Cohort Equations (PCE). 13Due to incomplete antihypertensive medication data and the fact that the only systolic blood pressure available was taken during hospitalization for STEMI, the values for systolic blood pressures for all patients were imputed via the following criteria: (1)   130 mmHg-no history of hypertension, (2) 135 mmHg-a history of hypertension and also on a beta-blocker, angiotensin-convertingenzyme inhibitor, or angiotensin receptor blocker, (3) 145 mmHg-a history of hypertension and not on any of the aforementioned medications.Data were also imputed for missing lipid profile values.
A sensitivity analysis was performed without imputation which excluded individuals with missing data, as their ASCVD risk could not be calculated.All statistical analyses were performed with RStudio version 4.2.3. 14Multiple imputation using the mice package in R was used to deal with missingness in the PCE variables. 15ndividuals were classified into three groups, statin recommended, statin considered, or statin not recommended according to the 2019 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on the primary prevention of cardiovascular disease and the 2022 US Preventive Services Task Force (USPSTF) guidelines on statin use for the primary prevention of cardiovascular disease in adults. 13,16This classification incorporated both the 10-year ASCVD risk according to the PCE, as well as clinical factors including a history of ASCVD, diabetes, smoking, hyperlipidemia, hypertension, family history of CAD, and LDL-C levels.

| RESULTS
A total of 821 patients met inclusion criteria for this sample.Of these, 186 patients (23%) had a nonatherosclerotic etiology of their STEMI, leaving 635 patients with STEMI due to atherosclerotic disease available for analysis.The majority of the cohort were men (82.4%) and identified as white (89%) (Table 1).The median age was 46.0 [42.0-48.0]years, with a heavily left-skewed distribution of 524 patients (83%) age 41-50 years, while only 8 (1.3%) were age 21-30 years.The median BMI was 29.0 [26.0-33.0]kg/m 2 in men and slightly higher in women (31.0 [27.2-36.0]kg/m 2 ).Systolic blood pressure on admission was similar in both genders.The most prevalent risk factors were current smoking (59%), hyperlipidemia (44%), and hypertension (37%).Nearly threequarters of the cohort were either current or former smokers (74%).A family history of CAD was also prevalent in over half of the cohort (52%).
In comparison, diabetes was not as prevalent (13%), with a median hemoglobin A1c of 5.80 [5.40-6.80]%, although it was more prevalent in women (22%) than in men (11%) (p = .001).A small proportion had a history of CAD (11%), while a history of stroke was rare (1.3%); rates did not differ between genders.
Rates of preventative medication use were higher when stratified by the relevant risk factor.Overall, 72% of individuals with a history of CAD were taking aspirin before admission.However, only 32.7% of individuals with a history of hyperlipidemia were on a statin and 34.8% of individuals with a history of hypertension were on an ACEi/ARB.Rates of aspirin, statin, and ACEi/ARB use were lower in individuals without the relevant risk factor (12.6%, 32.7%, and 2.0% respectively) (Figure 1).2).The sensitivity analysis included 505 individuals, with a similar percentages assigned to each statin recommendation group for both the 2019 ACC/AHA guidelines and 2022 USPSTF guidelines analyses (Supporting Information: Table 1).

| DISCUSSION
We performed a retrospective analysis of a prospective cohort of 635 patients aged ≤50 years who presented with STEMI due atherosclerotic disease to examine the clinical characteristics, risk factors, medication use, and statin eligibility based on the most recent guidelines for this population.The most prevalent risk factor was smoking, followed by hyperlipidemia and hypertension.Diabetes and drug use were relatively uncommon.Median LDL was not significantly elevated in the cohort and approximately half of young individuals experiencing STEMI were not eligible for statin therapy before their event.

| Comparison to YOUNG-MI registry
Prior cohorts have examined MI in younger adults.The Partners YOUNG-MI registry retrospectively examined a cohort of 2097 patients aged ≤50 years who presented with MI. 17 While this cohort included patients with NSTEMI and patients with nonatherosclerotic coronary disease (spontaneous coronary artery dissection, MI with nonobstructive coronary arteries), many of its findings mirror our analysis.Most of the patients were men at 80.7%.Hyperlipidemia, smoking, and hypertension were the most prevalent risk factors at 91.1%, 50.8%, and 47.8%, respectively.Only 19.8% of the cohort had diabetes at the time of their admission and rates of drug use (cocaine  Health and Nutrition Examination Survey, the prevalence of hypertension was somewhat lower in this cohort (36.7% vs. 46.7%)while the prevalence of hyperlipidemia was somewhat higher (44.2% vs. 34.7%). 18Diabetes was similarly prevalent in both groups (12.9% vs.
14.1%).Total cholesterol in this cohort was similar to that in adults ≥20 years (189.0 vs. 187.2mg/dL), however, HDL-C was lower (35.4 vs. 53.6 mg/dL) and triglycerides were higher (148 vs. 91.6 mg/dL).HDL-C was similar in both current smokers and never smokers in our cohort (36.0 vs. 37.2 mg/dL, p value = .325),suggesting that the lower HDL-C is not secondary to cigarette smoking. 19Further, only 11 individuals had an LDL-C ≥ 190 mg/dL, suggesting that familial hyperlipidemia was not significantly prevalent in our cohort.
In contrast, the rates of current smoking were substantially higher in this cohort than in adults ≥20 years.According to data from the 2020 National Health Interview Survey, only 12.5% (95% CI, F I G U R E 1 Preventative medication use by relevant risk factor and gender.Individuals with missing data were excluded from this analysis: aspirin (155), statin (156), ACEi/ARB (76).
four to fivefold higher rates of smoking compared to the general adult population. 20

| AMIYA and BMC2 studies
Further evidence that smoking may play a crucial role in STEMI secondary to atherosclerotic coronary disease in younger adults comes from an interesting cohort from India. 21Notably, only patients aged ≤30 years with STEMI were included in the study.In total, it included 1116 patients over a 2-year period with a mean age of 26.3 years.Smoking was the most prevalent risk factor in the cohort at 78.5%.The next most prevalent was a family history of premature CAD at 46.8%, followed by hyperlipidemia at 21.2% hypertension at 20.5%, and diabetes at 17.2%.On coronary angiography, 80.6% had obstructive atherosclerotic CAD, while another 12.2% had The odds ratio for smoking for individuals in the registry was 3.4 (95% CI 3.3-3.4),while the odds ratio for smoking for individuals aged 18-34 was 11.4 (95% CI, 10.0-12.8),when compared to the general population matched for age. 22

| Preventative medication use
The use of preventive medications before MI in our cohort was low.
These rates appear to be similar when compared to prior cohorts.In a Norwegian cohort of individuals aged <45, conducted from 2013 to 2016, only 12% of individuals were on aspirin, 13% were on a statin, 10% were on a beta blocker, and 11% were on an ACEi/ARB. 23When stratified by the relevant risk factor, rates of preventative medication use were substantially better.For example, most individuals with a history of CAD were on aspirin before admission, while a small minority of those without a history of coronary heart disease were on aspirin (Figure 1).This trend was also observed in individuals with hyperlipidemia and hypertension.5][26] This may be in part due to the 2013 ACC/AHA guidelines expanding statin eligibility by recommending the use of the PCE, rather than just LDL-C levels to determine statin eligibility. 27,280][31][32][33]

| Statin eligibility
Nearly half of the individuals in the present analysis were classified as statin not recommended according to the 2019 ACC/AHA 2019 guidelines. 13The most common reason for this classification was a It was instituted in 2003, standardizing the timely treatment of patients with STEMI who present to any of the included hospitals, regardless of percutaneous coronary intervention (PCI) capabilities.Inclusion criteria were new ST-elevation or new left bundlebranch block on electrocardiogram with chest pain <24 h in duration.There were no exclusion criteria, including age.Patient data are collected in a prospective and standardized database for quality improvement and clinical research purposes.Follow-up data is collected for a period of 5 years following the index admission.We examined all patients aged 50 or younger from this database from March 2003 to June 2021.Clinical documentation and the initial catheterization report for each individual

4. 2 |
Comparison to 2017-2020 NHANES While cardiovascular risk factors are prevalent throughout the cohort, examining them in light of the prevalence of risk factors in the general adult population in the United States yields additional insights.When compared to data in adults ≥20 years from the 2017-2020 National Baseline characteristics, medical history, home medications, and drug use on admission.
Lipid profile by gender.
Statin eligibility of STEMI patients under 50 according to the 2019 American College of Cardiology/American Heart Association and the 2022 US Preventive Services Task Force statin guidelines.
395][36][37]ing in risk stratificationThe benefit of noninvasive imaging for ASCVD risk stratification in younger adults is unclear.Coronary artery calcium scoring can be used to quantify calcified coronary plaques, however, younger individuals are more likely to have noncalcified plaque, even when presenting with acute coronary syndrome.[35][36][37]Asecondaryanalysis of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain trial examined the use of coronary computed tomography angiography (CTA) in risk stratification.38Itincluded3986patientsaged60.5 ± 8.2 years and calculated statin eligibility by incorporating coronary CTA findings into the PCE risk model.In statin naïve patients, this approach did improve the overall discrimination of the risk model.Event rates in statin eligible patients increased from 3.4% to 4.0% and decreased in statin non-eligible patients from 2.7% to 2.1%, when incorporating coronary CTA findings.However, this was largely due to the appropriate downward reclassification of approximately 17% the cohort from statin eligible to statin not-eligible.Hence, coronary CTA may not provide the incremental risk stratification to appropriately reclassify younger adults as higher risk for ASCVD.An alternative clinical model for assessing longer-term ASCVD risk in younger adults was proposed by Pencina et al.39They followed 4506 individuals aged 20-59 without prior ASCVD, from the Framingham Offspring cohort.Male gender, age, smoking, systolic blood pressure, antihypertensive treatment, diabetes, total cholesterol positively correlated with a 30-year ASCVD risk while HDL-C had a negative correlation.These correlations remained significant when adjusting for changes in risk factors over time.Building on this, Stone et al. proposed adopting a 30-year risk screening protocol in adults aged 20-39 years.
40If smoking, hypertension, family history of premature ASCVD, severe hyperlipidemia or familial hyperlipidemia, diabetes, or other persistent major enhancing risk factors are present, they proposed pursuing intensive lifestyle and pharmacological interventions as appropriate.